Introduction:
L-gulonolactone oxidase (Gulo) is the rate limiting enzyme for Vitamin C (VitC) biosynthesis. Humans rely on dietary VitC for collagen synthesis, extracellular matrix formation, and tissue regeneration. VitC deficiency is an unrecognized condition and its role in cardiac homeostasis and post-acute myocardial infarction (AMI) remodeling is unknown.
Hypothesis:
Low levels of VitC impair cardiac function and tissue repair following AMI.
Methods:
Adult male Gulo
-/-
knockout mice (C57BL6 background, N=8) and control C57BL (N=8), which are able to synthesize VitC were used. VitC deficiency was maintained supplying low levels of VitC (30mg/l) to Gulo
-/-
mice in drinking water. Mice underwent M-mode and Doppler echocardiography to measure left ventricular (LV) diameters and wall thicknesses, fractional shortening (FS), E and A waves, E/A ratio, isovolumetric relaxation time (IRT) and myocardial performance index (MPI). Experimental AMI was induced by coronary artery ligation for 7 days. An additional group of Gulo
-/-
were mice supplemented with physiological levels of VitC (330 mg/l) and underwent AMI.
Results:
VitC deficient Gulo
-/-
mice exhibited significantly reduced LV wall thicknesses, reduced FS, and impaired diastolic function, measured as significantly reduced E/A ratio and longer IRT (Panel A, B & C). Following AMI, 100% (8/8) of deficient Gulo
-/-
mice died within 5 days. Supplementation with physiological levels of VitC significantly improved survival after AMI (Panel D).
Conclusion:
VitC deficiency impairs systolic and diastolic function. Moreover, VitC is critical for the post-AMI survival.
K042 Relationship between systolic and diastolic blood pressure and left ventricular systolic and diastolic function in patients with essential hypertension
